Pain is the most common clinical symptom. It is a complex phenomenon, having both a sensory-discriminative component, and a strong, reactive, motivational-affective dimension. Cortical processing of pain is poorly understood. Previous studies indicate an involvement of additional cortical regions. The ventrolateral orbital cortex (VLO) is the principal efferent target of medial thalamic areas recently suggested to be involved in nociception, especially its motivational-affective components. Our preliminary data indicate that some VLO neurons do respond to painful stimuli, and that their responses are most pronounced when tonic type of stimuli, which evoke a strong motivational-affective reaction (e.g., cold pressor), are applied. This application proposes to further investigate the role VLO neurons might have in nociception and pain perception. Response characteristics of these neurons to various stimuli (including tonic pain, and chronic pain induced by sciatic ligation mononeuropathy) will be assessed in conventional extracellular single-unit recordings. Response characteristics following systemic administration of clinically useful drugs morphine and amitriptyline, or iontophoretic application of morphine, serotonin, and norepinephrine, will also be examined. For comparison, the same type of experimental paradigms will be employed in similar recordings from S1. The results of the proposed study should provide both, a better understanding of how the VLO participates in nociception and serve as a basis for further investigations of cortical involvement in pain.